Search

Excessive fructose diet is closely associated with colorectal cancer (CRC) progression. Nevertheless, fructose's specific function and precise mechanism in colorectal cancer liver metastasis (CRLM) is rarely known. Here, this study reported that the fructose absorbed by primary colorectal cancer could accelerate CRLM, and the expression of KHK-A, not KHK-C, in liver metastasis was higher than in paired primary tumors. Furthermore, KHK-A facilitated fructose-dependent CRLM in vitro and in vivo by phosphorylating PKM2 at Ser37. PKM2 phosphorylated by KHK-A inhibited its tetramer formation and pyruvic acid kinase activity but promoted the nuclear accumulation of PKM2. EMT and aerobic glycolysis activated by nuclear PKM2 enhance CRC cells' migration ability and anoikis resistance during CRLM progression. TEPP-46 treatment, targeting the phosphorylation of PKM2, inhibited the pro-metastatic effect of KHK-A. Besides, c-myc activated by nuclear PKM2 promotes alternative splicing of KHK-A, forming a positive feedback loop.

Excessive fructose diet is closely associated with colorectal cancer (CRC) progression. Nevertheless, fructose's specific function and precise mechanism in colorectal cancer liver metastasis (CRLM) is rarely known. Here, this study reported that the fructose absorbed by primary colorectal cancer could accelerate CRLM, and the expression of KHK-A, not KHK-C, in liver metastasis was higher than in paired primary tumors. Furthermore, KHK-A facilitated fructose-dependent CRLM in vitro and in vivo by phosphorylating PKM2 at Ser37. PKM2 phosphorylated by KHK-A inhibited its tetramer formation and pyruvic acid kinase activity but promoted the nuclear accumulation of PKM2. EMT and aerobic glycolysis activated by nuclear PKM2 enhance CRC cells' migration ability and anoikis resistance during CRLM progression. TEPP-46 treatment, targeting the phosphorylation of PKM2, inhibited the pro-metastatic effect of KHK-A. Besides, c-myc activated by nuclear PKM2 promotes alternative splicing of KHK-A, forming a positive feedback loop. Upregulated KHK-A promoted the phosphorylation and nuclear translocation of PKM2 in colorectal cancer. Nuclear PKM2 promoted EMT, aerobic glycolysis, CRLM and alternative splicing of KHK-A. [Display omitted] [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer with poor prognosis. This study designated to figure out the effects of Ubiquitin Specific Peptidase 36 (USP36) on NSCLC. Data of this study demonstrated that upregulation of USP36 was observed in NSCLC tissues and cell lines. Overexpression of USP36 promoted NSCLC cell proliferation and inhibited NSCLC cell apoptosis. Knockdown of USP36 decreased Ketohexokinase A (KHK-A) and increased KHK-C expression at both RNA and protein levels. Expression of c-MYC and hnRNPH1/H2 was positively correlated with the expression of USP36. Upregulation of c-MYC reversed the downregulation of hnRNPH1/H2 induced inhibition of USP36. Overexpression of hnRNPH1/H2 reversed the downregulation of KHK-A induced inhibition of USP36. Results of in vivo xenograft model were consistent with the findings of in vitro experiments. In summary, overexpression of USP36 in NSCLC accelerated tumor growth through upregulation of KHK-A, which was medicated by stabilizing c-MYC to increase hnRNPH1/H2 expression. [ABSTRACT FROM AUTHOR]